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Front Neurosci. 2010 Jul 8;4:52. doi: 10.3389/fnins.2010.00052. eCollection 2010.

Central tetrahydrobiopterin concentration in neurodevelopmental disorders.

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Department of Pediatrics, Division of Child and Adolescent Neurology and The Children's Learning Institute, University of Texas Health Science Center Houston, TX, USA.


Tetrahydrobiopterin (BH(4)) is a naturally occurring cofactor essential for critical metabolic pathways. Studies suggest that BH(4) supplementation may ameliorate autism symptoms; the biological mechanism for such an effect is unknown. To help understand the relation between central BH(4) concentration and systemic metabolism and to develop a biomarker of central BH(4) concentration, the relationship between cerebrospinal fluid BH(4) concentration and serum amino acids was studied. BH(4) concentration was found to be distributed in two groups, a lower and higher BH(4) concentration group. Two serum amino acids, citrulline and methionine, differentiated these groups, and the ratio of serum citrulline-to-methionine was found to correlate with the cerebrospinal fluid BH(4) concentration (r = -0.67, p < 0.05). Both citrulline and methionine are substrates in inflammation and oxidative stress pathways - two pathways that utilize BH(4) and are abnormally activated in autism. These data suggests that central BH(4) concentration may be related to systemic inflammation and oxidative stress pathways.


autism; inflammation; oxidative stress; serum amino acids; tetrahydrobiopterin

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